Race and Ethnicity Representation in Phase 2/3 Oncology Clinical Trial Publications

Key Points Question What are the race and ethnicity reporting rates and representation quotients in published oncology clinical trials? Findings In this systematic review of 364 phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Meaning The findings of this study support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act–concordant race and ethnicity federal reporting requirements.


Introduction
Randomized clinical trial publications remain the standard for informing evidence-based treatment recommendations. 1 However, oncology clinical trial enrollment has not reflected the diversity of the US population, 2 even though patients from marginalized groups underrepresented in clinical trials accept invitations to participate in clinical trials if appropriately engaged. 3Ultimately, a lack of racial and ethnic diversity in published clinical trials challenges the generalizability of outcomes and can perpetuate health disparities by adversely affecting clinical practice guidelines. 4 2010, the Affordable Care Act (ACA) Section 4302 required the US Department of Health and Human Services to establish race and ethnicity data collection and reporting standards, which adopted 5 federally defined race and ethnicity definitions per the 1997 Office of Management and Budget standards. 5To our knowledge, no study has evaluated oncology clinical trial representation across the 5 racial categories, specifically including American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander populations.Therefore, the objectives of this study were to quantify race and ethnicity reporting rates from 4 high-impact medical journals and examine patient representation by race and ethnicity compared with national cancer incidence.

Methods
In a systematic review, published phase 2/3 oncology clinical trials were evaluated in 4 high-impact journals (by Google Scholar/SCImago rankings): JAMA, Journal of Clinical Oncology (JCO), Lancet, and New England Journal of Medicine (NEJM), published between January 1, 2012, and December 31, 2022.
The most common US noncutaneous solid cancers were included.Primary outcomes were race and ethnicity reporting rates and publication representativeness.Publications were excluded for not being phase 2/3 trials, having an international first author, evaluating multiple cancers, or not evaluating cancer treatment.Publications were assessed by 2 or more reviewers.This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Statistical Analysis
Representation quotients (RQs) were calculated by dividing the proportion of published patients by the proportion of year-matched, site-specific, US incident cancers.An RQ less than 1 signifies race or ethnicity underrepresented based on Cancer in North America data.Kruskal-Wallis tests with Bonferroni correction (BC) compared RQs.Multivariable logistic regression evaluated factors associated with race and ethnicity reporting, presented as adjusted odds ratios with 95% CIs.Journal publication race and ethnicity reporting and ClinicalTrials.govfederal entries were compared using the McNemar χ 2 test with continuity correction (P MC).Analyses were performed using R, version

Discussion
To our knowledge, we conducted the first analysis of oncology clinical trial representation according to federal standards, including American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients.Among the 5 racial and ethnic categories, Asian and White participants were most frequently reported, while American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients were least reported.Moreover, American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander representativeness was not merely low, but 0 among published oncology clinical trials assessed.Our findings support a call-to-action for medical researchers to uphold policies that adhere to ACA-concordant reporting requirements to prevent erasure of Indigenous health disparities. 6erican Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients are known to have the lowest life expectancy in the US and face underrecognized health disparities. 68][9] American Indian or Alaska Native patients living on reservations face barriers to clinical trials, including long travel times, lodging expenses, and conflicts between Western medicine and traditional healing knowledge. 9Native Hawaiian or Other Pacific Islander patients in the Pacific live thousands of miles away from cancer facilities.
Adoption of patient health navigators and community health workers has great potential to help facilitate coordinated continuity of care for patients with cancer who are eligible for clinical trials.American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander data omission is a form of structural racism that perpetuates Indigenous health disparities. 8,10By adhering to ACA-concordant race and ethnicity reporting requirements, medical journals have the opportunity to promote transparent, consistent, and accurate data reporting for the most marginalized populations.
With limited attention to Indigenous inclusion and representation in clinical trials, there is a clear need for funding and innovative strategies to improve Indigenous clinical trial enrollment.
Our analysis echoes more than 3 decades of previous studies that show that Black or African American and Hispanic patients remain consistently underrepresented in cancer clinical trials, persisting even after US Food and Drug Administration approval. 2,11,12Clinician-imposed selection bias is also known to contribute to disproportionate race and ethnicity representation in clinical trials. 13Broadening selection criteria to include a wider range of prognosis or comorbidity burden may also increase clinical trial enrollment across diverse populations. 14,15

Strengths and Limitations
Strengths of this study include the inclusion of all 5 ACA-concordant race and ethnic reporting categories, the comprehensive nature of the RQ analysis across 6 major cancers, and the use of the Cancer in North America dataset for standardization of national cancer incidence.This study has limitations.First, a major limitation is that, while inclusive of more than 97% of the US population, large cancer databases, including the Cancer in North America database, substantially underestimate American Indian and Alaska Native cancer incidence given the lack of integration within the Indian Health Service or cross-validation with Tribal systems; nonetheless, the 0.00 American Indian and Alaska Native RQ would likely persist.Second, we used US cancer incidence, which may have skewed international trials, which was the rationale for our sensitivity analyses suggesting a consistent finding among the US-only studies.Third, we focused on 4 journals and acknowledge the inclusion of other journals may improve generalizability.Improving race and ethnicity reporting at these highimpact journals could set new standards and motivate trialists to improve their race and ethnicity collection and reporting practices.

JAMA Health Forum | Brief Report
4.0.3 in RStudio, version 1.3.1093(R Foundation for Statistical Computing).

Table 1 and the Figure show
the race and ethnicity reporting overall and stratified by journal.

Table 1 .
Characteristics of Phase 2/3 Oncology Clinical Trials Published in JAMA, JCO, Lancet, and NEJM the oncology clinical trial publications, with race and ethnicity reporting generally highest in JAMA and lowest in NEJM.Reporting varied by race and ethnicity from 28 (8%) for Other Pacific Islander populations to 254 (70%) for the White populations.
Abbreviations: JCO, Journal of Clinical Oncology; NEJM, New England Journal of Medicine.aThe trial design variables are independently recorded as binary yes or no (not mutually exclusive).across

Table 2
and eFigure 2 in Supplement 1 display the median RQ of phase 2/3 US oncology clinical trial publications, which was lowest across all cancers among both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients at 0.00 (IQR, 0.00-0.00)and highest among Asian patients at 1.04 (IQR, 0.09-4.77;P < .001BC).Median RQ for Hispanic patients was 0.60 (IQR, 0.37-0.82),which was lower than non-Hispanic patients at 1.04 (IQR, 1.01-1.06;P < .001BC).Across race, all cancer sites had significantly different RQs (P < .001BC) except for endometrial cancer.For Hispanic ethnicity, RQs were significantly different for breast, colorectal, and prostate (P < .05BC) cancers.Multivariable regression found US-based trials were most likely to publish race and ethnicity (adjusted odds ratio, 1.67; 95% CI, 1.01-2.80)(eTable 1 in Supplement 1).Disparities in race and Figure.Proportion of Phase 2/3 Cancer Clinical Trial Publications That Report Race and Ethnicity Published in the Journal of Clinical Oncology (JCO), JAMA, Lancet, and the New England Journal of Medicine (NEJM) Between 2012 and 2022

Table 2 .
Representation Quotients of Published Phase 2/3 Cancer Clinical Trials by Cancer Site and Race and Ethnicity a Representation quotients are calculated from the proportion of patients by race and ethnicity enrolled in a published clinical trial divided by the reported United States North American Association of Central Cancer Registries (NAACCR) Cancer in North America year-matched site-specific cancer incidence by race.A representation quotient of 0 signifies race or ethnicity without any published representation relative to Cancer in North America data.Representation quotients of 1 represent equal representation in a clinical trial compared with expected US NAACCR year-matched site-specific cancer incidence.P values were calculated using the Kruskal-Wallis rank-sum test.ethnicity reporting persisted within the US-only subset sensitivity analysis.American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander race was reported less in journal publications compared with ClinicalTrials.gov(P < .001MC) (eTable 2 in Supplement 1). a